The purpose of this competing continuation grant proposal is to continue developing and evaluating methodological and statistical procedures to determine how prevention programs change outcome variables. These mediation analyses assess the link between program effects on the constructs targeted by a prevention program and effects on the outcome. As noted by many researchers, mediation analyses identify the most effective program components and increase understanding of the underlying processes leading to changing outcome variables. The need for these new procedures became apparent in the analyses of several NIDA funded drug prevention programs. The Principal Investigator of this grant received a one-year NIDA funded small grant to study the assessment of mediation effects and a four-year grant to develop and evaluate methods and statistical procedures for the types of designs and procedures commonly used in prevention research. The proposed four-year continuation study will examine three statistical topics that represent the next steps in this research. Each statistical study includes analytical and simulation research as well as applications to actual etiological and prevention data. In Study 1, significance testing using resampling methods and methods based on the distribution of the product of two random variables will be developed and evaluated. New tests for mediation will also be evaluated in this study. Study 2 will investigate mediation models for program effects that differ by subgroups of participants. One of these models is the mediated baseline by treatment moderator model where program effects depend on baseline levels of a mediating variable. Study 3 will continue the development and evaluation of mediation methods in latent growth curve modeling including models identifying groups or classes of study participants with different trajectories of change over time. In Study 4, the statistical methods will be applied in several NIH funded prevention data sets providing important feedback about the usefulness of the models. Study 5 will disseminate new information about mediation analysis including the development of a mediation analysis working group and additions to our mediation analysis website.